title: Lidocaine suppresses the increased extracellular signal-regulated kinase/cyclic AMP response element-binding protein pathway and pro-inflammatory cytokines in a neuropathic pain model of rats.
abstract: OBJECTIVE
  Rats which have undergone spinal nerve ligation (SNL) display increases in the expression of extracellular signal-regulated kinase (ERK 1/2) and cyclic AMP response element-binding (CREB) protein. The present study was designed to determine whether lidocaine has a beneficial effect on the treatment of neuropathic pain by analysing related proteins.
  
  
  METHODS
  Twenty-four male Sprague–Dawley rats were randomly allocated to three groups (eight per group): shamoperated (control) group, a neuropathic pain and normal saline group (NP+NS), a neuropathic pain and lidocaine group (NP+Lido, 2mgkg(-1) h(-1)). Anaesthetised rats received left L5 and L6 SNL. The mechanical withdrawal threshold test was performed 7 days after SNL and for 7 days with the pump implanted (saline or lidocaine). At post-implanted pump day 7, their brains and spinal cords were harvested. ERK 1/2, CREB proteins and mRNA amounts of pro-inflammatory cytokines (tumour necrosis factor a, intercellular adhesion molecule 1, monocyte chemo-attractive protein 1 and macrophage inflammatory protein 2) were assessed by immunoblotting or reverse transcriptase-PCR on samples collected from the three groups.
  
  
  RESULTS
  Lidocaine increased the mechanical withdrawal threshold of a neuropathic rats. In only spinal tissues, ERK 1/2 and CREB proteins in the NP+Lido group was significantly reduced to 39%, and 48% in comparison with the NP+NS group. The NP+Lido group showed a significant reduction in mRNA amounts of pro-inflammatory cytokines compared with the NP+NS group (P<0.05).
  
  
  CONCLUSIONS
  These results suggest that lidocaine therapy may be effective in treating neuropathic pain after spinal nerve injury, and that these effects may occur via suppression of ERK 1/2 and CREB signalling proteins and anti-inflammatory effects.
authors.affiliation: Saint Vincent Hospital, the Catholic University of Korea, Suwon, Korea.
authors.forename: Jin D
authors.initials: JD
authors.lastname: Joo
authors.forename: Jin W
authors.initials: JW
authors.lastname: Choi
authors.forename: Jang H
authors.initials: JH
authors.lastname: In
authors.forename: Hong S
authors.initials: HS
authors.lastname: Jung
authors.forename: Jung A
authors.initials: JA
authors.lastname: Lee
authors.forename: Yong S
authors.initials: YS
authors.lastname: Kim
authors.forename: Dae W
authors.initials: DW
authors.lastname: Kim
authors.forename: Je H
authors.initials: JH
authors.lastname: Yeom
authors.forename: Eun Y
authors.initials: EY
authors.lastname: Shin
authors.forename: Yeon S
authors.initials: YS
authors.lastname: Jeon
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000378:metabolism; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects / Q000378:metabolism; D009437:Neuralgia / Q000188:drug therapy*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000779:Anesthetics, Local; D017362:Cyclic AMP Response Element-Binding Protein; D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; D008012:Lidocaine; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3